We propose to prospectively assess the association of low-penetrance polymorphisms and haplotypes in candidate DNA repair genes to the risk for melanoma and non-melanocytic skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the Nurses' Health Study. We hypothesize that candidate polymorphisms and haplotypes in three important DNA repair genes (XPD in nucleotide excision repair; XRCC1 in base excision repair; XRCC3 in homologous recombination repair) are associated with higher risk of skin cancer. We will further examine whether the candidate polymorphisms modify the association between the sunlight exposure and the risk of skin cancer. After blood collection in 1989-90 up to 1998, we have accrued 743 incident cases of skin cancers (177 melanoma, 283 SCC, and 283 BCC which were randomly selected from diagnosed BCC cases); each case will be matched by age and race to a control in the nested case-control study. We will have >90% power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and lifetime sunlight exposure. This study will be among the first studies of the association of polymorphisms in candidate DNA repair genes with skin cancer, which assess potential interactions between genotype and sunlight exposure.